DESCRIPTION: Applicant's Abstract S. aureus is the most common cause of infections in drug users and is a major cause of life-threatening infections in AIDS patients. Surprisingly little is known about the factors that predispose these two overlapping groups to staphylococcal disease. Drug users and HIV-infected subjects have a high S. aureus colonization rate and are believed to become infected with the strains they carry. This proposal will integrate a molecular epidemiologic analysis of S. aureus colonization and infection in these high risk groups with a biologic investigation of the basis for this process. By targeting patients less than 60 admitted to the hospital, we will focus on HIV-infected drug users in a case series. Endpoints will include evidence of S. aureus colonization or infection. The goals include the following. 1) Identify the factors, such as patterns of drug use, HIV status and form of medical intervention, that maximally increase the risk of S. aureus infection. 2) Use DNA fingerprinting techniques to determine whether: strains that colonize also cause infection; carriage is clonal; hospitalization affects carriage or acquisition of new strains; there is clonal spread of strains among enrolled subjects including HIV-infected, drug users or controls as well as hospital personnel. 3) Determine the impact of hospitalization and antimicrobial therapy on the emergence of multidrug resistant staphylococci including whether antibiotic therapy alters colonization or infection or the susceptibility patterns of colonizing strains. Investigate if there is linkage of other virulence determinants with drug resistance or if there is evidence of clonal spread of resistant isolates among the cohort or hospital personnel. 4) Identify if specific determinants are critical to colonization, and if their presence is associated with sites of colonization and pattern of drug use. The emerging problems of multidrug-resistant staphylococci has added urgency to the need for new, nonantimicrobial approaches to the prevention of these life-threatening diseases. In order to develop alternatives, we must first - be able to identify when high risk individuals are at maximal risk of infection and, second - sufficiently understand the strain and host determinants that play a critical role in this process. The ability to integrate both epidemiologic and biologic studies using a well defined high risk cohort of drug users and HIV-infected subjects provides an ideal setting to examine these issues.